Effects of cholecystokinin on morphine-elicited hyperactivity in hamsters.

The effects of the octapeptide cholecystokinin (CCK) on hamster locomotor activity were investigated in three experiments. In Experiment 1, the effect of CCK (25, 50, 75 micrograms/kg) on morphine (2.5 mg/kg)-elicited hyperactivity was studied. Results indicated that CCK antagonized morphine-elicited hyperactivity and that CCK alone elicited hypoactivity. There were no effects of dose of CCK. In Experiment 2, the effects of intraperitoneal (IP) and subcutaneous (SC) routes of administration of CCK (25 micrograms/kg) on locomotor activity were studied. Compared to saline controls, CCK induced hypoactivity that was of greater magnitude and of longer duration when administered IP than SC. Experiment 3 was designed to replicate the route of administration effect observed in Experiment 2 and to determine whether sensitization to CCK-induced hypoactivity develops over the course of a few injections. Results indicated that CCK-induced hypoactivity was greater after IP than SC administration but that sensitization was not detectable. It is concluded that CCK antagonizes morphine-elicited hyperactivity in the hamster by acting, in part, independently of morphine to produce opposite behavioral effects.

Cholecystokinin-induced satiation with ethanol: effects of lighting cycle and limited access procedures.

Cholecystokinin (CCK) is a brain-gut neuropeptide and hormone previously shown to inhibit alcohol intake in water- or food-deprived rats. The effects of CCK and the phase of lighting cycle on alcohol intake in rats were investigated in a comparison of limited access and water-restriction procedures. The limited access procedure (LAP) is a recently developed technique for inducing free-choice alcohol consumption in nondeprived animals. Two groups of 12 male rats each were maintained in either normal or reversed 12:12 L:D lighting cycles and simultaneously given 40 minutes' access to 6% w/v ethanol and water in nonhome cages. After adaptation to this procedure, CCK octapeptide (0.5-16 micrograms/kg) was injected IP prior to access to fluids. During LAP, CCK reduced alcohol intake and increased water intake more potently in the dark phase. These effects of CCK were more reliable when the design was replicated, which suggests the importance of acquired expectancies for the development of CCK's actions. CCK more effectively reduced alcohol intake in LAP, than in a 23.3-h water-deprivation procedure for inducing alcohol intake in a 2-bottle choice test with water. However, CCK was less so effective in LAP, than in the water-deprivation procedure when alcohol was presented alone in a 1-bottle test. The alcohol satiation effect of CCK is independent of prior deprivation and not an artifact of thirst reduction, debilitation, or conditioned aversion, because CCK strongly increased water intake in the limited access procedure, and ethanol preference remained robust after experience with CCK. CCK may operate endogenously as a specific factor in satiation with ethanol.

Vasoactive intestinal peptide: behavioral effects in the rat and hamster.

The behavioral effects of intracerebroventricular (ICV) injection of the brain-gut peptide vasoactive intestinal peptide (VIP) were quantified with a behavioral sampling technique in home-caged, nondeprived, male and female albino rats and golden hamsters. ICV VIP sex-dependently decreased observed resting behavior during 1 hr after injections in both rats and hamsters at 0.1-10.0 micrograms. Grooming behavior was increased in hamsters, and rearing and standing behaviors were increased in rats, sex-dependently at VIP doses that decreased resting. Drinking behavior was suppressed in rats by VIP at 10.0 micrograms. Intraperitoneal (IP) VIP (100.0 micrograms/kg) increased 5% ethanol intake and decreased eating behavior in fluid-deprived male rats. The increase in ethanol intake produced by IP VIP was prevented by IP cholecystokinin octapeptide (CCK, 4.0 micrograms/kg). VIP potently controls resting and ingestive behaviors, suggesting a role for this neuropeptide, along with CCK, in the feedback regulation of rodent behavior.

Cholecystokinin and satiation with alcohol.

Release of the brain-gut peptide cholecystokinin (CCK) is stimulated by intragastric instillation of ethanol, and peripheral administration of CCK inhibits ethanol consumption. To assess the temporal specificity of the inhibitory effect of CCK on alcohol intake, water-deprived rats were given 5% ethanol at 20, 10 or 0 min after intraperitoneal injections of CCK octapeptide. Delaying access to ethanol for 20 min prevented a significant effect of CCK on intake. CCK's temporally constrained inhibitory action on alcohol consumption is consistent with an ethanol satiation effect. To test the motivational specificity of CCK's effect on fluid intake, rats were allowed a 2-bottle choice of 2% ethanol and water after CCK injections. Ethanol solution intake was suppressed by CCK, and total water intake was unaffected. The putative alcohol satiation action of CCK is appropriately specific to ethanol solution in free-choice tests. Hungry, but not fluid-deprived rats that were either ethanol experienced or naive received a 2-bottle choice of 4% ethanol or water after CCK or saline injections. CCK again specifically inhibited ethanol intake, but this effect required prior ethanol experience. Doses of CCK and naloxone, an opioid receptor blocker, combined to inhibit ethanol intake in an infra-dose-additive manner in water-deprived rats. CCK may act endogenously, in part on opioid receptor-mediated processes, as a preabsorptive satiety signal of ethanol. The full expression of this action appears to depend on prior conditioning of nutritive expectancy of the postingestive effects of alcohol.

Bombesin-induced grooming in the golden hamster.

Lateral cerebroventricular injection of the peptide bombesin (0.01-1.0 micrograms) promptly elicited excessive grooming and scratching behaviors in home-caged male and female golden hamsters. Bombesin-induced grooming persisted throughout a 60-min observation period at doses of 0.1-1.0 micrograms. Grooming with forepaws and mouth was more consistently increased than hindleg scratching behaviors. Dependence of this neuropeptide effect on grooming on muscarinic cholinergic activity was assessed by injecting scopolamine (0.001-1 mg/kg) intraperitoneally 15 min prior to 0.1 microgram bombesin. Excessive grooming induced by centrally administered bombesin was abolished by 0.1 and 1 mg/kg scopolamine, although basal level of grooming was not significantly affected. The findings indicate a cross-species generality of the dependence of bombesin-induced grooming on muscarinic cholinergic activity, and species-specific differences among rodents in the components of excessive grooming elicited by bombesin.